Total synthesis and structure revision of gonioheptenolactone

Abstract

We report the first total synthesis and structure revision of the cytotoxic styryllactone gonioheptenolactone. The synthesis features a highly stereoselective epoxide formation followed by an intramolecular, regioselective nucleophilic epoxide-opening reaction to construct the key tetrahydrofuran skeleton. Our findings reveal that the originally proposed structure of gonioheptenolactone as an unsaturated eight-membered lactone is incorrect; the actual structure is revised to tetrahydrofuryl acrylate. The synthesized natural products, gonioheptenolactone and isoaltholactone, were evaluated for their in vitro antiproliferative activity against a panel of human tumor cell lines, providing further biological insights.